Proteins and peptides are widely employed for therapeutic purposes whether in their native forms, variant forms or analogues thereof. Protein therapeutics tend to be specific for their targets, leading to potentially fewer side effects, but often with lower bioavailability, poorer membrane permeability, and metabolic instability, as compared to small molecules. Protein-based drugs are generally referred to as ‘biologics’ and include molecules such as insulin, growth factors, and engineered antibodies.
Proteinaceous molecules typically require injection; nevertheless, biologics have been an extremely successful class of therapeutics including antibodies for treatment of arthritis and various cancers, soluble proteins for diabetes, myelosuppression and renal anemia; as well as short injectable peptides for multiple sclerosis, cancers, endometriosis and fibroids and acromegaly.
Peptides represent a class of molecules that have the specificity and potency of larger protein biologics, but are smaller in size and more accessible and cheaper to manufacture using chemical methods, thus potentially combining some of the advantages of proteins with those of small molecules.
Protein and peptide compounds can be modified in various ways in order to improve one or more features of the compound, or address one or more potential draw-backs of the compound. For example, a stabilizing peptide sequence may be added to the N- and/or C-terminus of pharmacologically active peptides potentially making them less susceptible to degradation (WO 99/46283). Further, a linear amino acid probe of 6 amino acids selected from Lys or Glu added to the N-terminus of α-MSH potentially increases efficacy compared to the native peptide (WO 07/22774). Known peptide-drug conjugates further include addition of polycationic peptides CPP (cell-penetrating peptides) to improve transport across the cell lipid bi-layer.